Cardiovascular disease (CVD) continues to be the leading cause of death in the United States and is associated with a growing economic and personal burden (1999 Heart and Stroke Statistical Update, Dallas, Tex.: American Heart Association, 1998). Despite numerous advances in modern medical treatments, the most effective strategy for combating the disease remains prevention. Research efforts since the 1960s have identified elevated total serum cholesterol and low-density lipoprotein-cholesterol (LDL-cholesterol) concentrations as powerful risk factors for CVD (Pocock and Shaper, Br. Med. J., 298, 998 (1989); National Cholesterol Education Program, Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II), Bethesda: National Institutes of Health, National Heart, Lung, and Blood Institute, National Cholesterol Education Program, 1993).
Additionally, observational studies and randomized trials have demonstrated a positive and continuous relationship between diastolic blood pressure (DBP) and CVD (MacMahon et al., Lancet, 335, 765 (1990); Collins et al., Lancet, 335, 827 (1990)). The age-adjusted prevalence of hypertension (systolic blood pressure (SBP) >140 millimeters mercury (mm Hg), or diastolic blood pressure >90 mm Hg, or use of hypertensive medication) among U.S. adults 20-74 years of age has been estimated to be 23% (Kramarow et al., Health and Aging Chartbook, Health, United States, Hyattsville: National Center for Health Statistics, 9, 222 (1999)). Reductions of as little as 5-6 mm Hg in diastolic blood pressure maintained over a 5-year period can decrease CVD risk by 20-25% and stroke risk by 35-40% (MacMahon et aL, Lancet, 335, 765 (1990)).
The National Cholesterol Education Program (NCEP) advocates diet therapy as the primary intervention for lowering serum cholesterol concentrations, whereas drug therapy is reserved only for those individuals not responding adequately to diet and who exhibit a high risk cardiovascular disease profile (National Cholesterol Education Program, Second Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II), Bethesda: National Institutes of Health, National Heart, Lung, and Blood Institute, National Cholesterol Education Program, 1993). Based on these guidelines, it has been estimated that 29% of all adults in the US would require dietary therapy (Sempos et al., JAMA, 269, 3009 (1993)).
Pharmacological therapy is generally recommended for the treatment of hypertension (The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, Arch. Intern. Med., 157, 2413 (1997)). Yet because of its cost and adverse side effects various dietary approaches to the treatment and prevention of hypertension have been gaining growing acceptance and popularity (Appel et al., N. Engl. J. Med., 336, 1117 (1997); Sacks et al., New Engl. J. Med., 344, 3 (2001); Eliasson et al., J. Hypertens., 10, 195 (1992)).
The use of viscous (soluble) fibers is one of the diet strategies shown to decrease serum cholesterol concentrations (Glore et al., J. Am. Diet. Assoc., 94, 425 (1994)). Based on data from controlled clinical trials it has been estimated that daily intake of 2-10 grams per day (g/d) of soluble fiber significantly decreases total and LDL-cholesterol (Brown et al., Am. J. Clin. Nutr., 69, 30 (1999)). Specifically, consumption of β-glucan-containing oat products leads to an average cholesterol reduction of 5.9 milligrams per deciliter (mg/dL) (Ripsin et al., JAMA, 267, 3317 (1992)). On the other hand, intake of insoluble, non-viscous fibers, such as cellulose, does not lower lipid concentrations (Truswell and Beynen, Dietary Fiber and Plasma Lipids: Potential for Prevention and Treatment of Hyperlipidemias, In: Schweizer and Edwards, eds., Dietary Fiber—A Component of Food, New York: Springer Verlag, 295-332 (1992)).
Besides a hypolipidemic effect, there is a growing body of literature suggesting that viscous (soluble) fibers also lower blood pressure (Keenan et al., Adv. Exp. Med. Biol., 427, 79 (1997)) and CVD risk in general (Anderson, Can. J. Cardiol., 11, 55G (1995); Anderson and Hanna, J. Nutr., 129, 145S (1999)). Soluble, dietary fiber consumption has been inversely related to hypertension (Ascherio et al., Circulation, 86, 1475 (1992)) and diastolic blood pressure (Ludwig et al., JAMA, 282, 1539 (1999)) and several intervention studies of viscous fibers have reported blood pressure reductions in both hypertensive and normotensive individuals (Wright et al., Br. Med. J., 2, 1541 (1979); Schlamowitz et al., Lancet, 2, 622 (1987); Singh et al., J. Hum. Hypertens., 7, 33 (1993); Saltzman et al., J. Nutr., 131, 1465 (2001)). However, the practical utility of viscous fibers as hypocholesterolemic and hypotensive agents is often limited by the lower gastrointestinal side effects associated with increased consumption and related to their fermentability.
As early as the 1960s individuals who secreted abnormally large amounts of insulin in response to dietary carbohydrate were shown to have high incidence of vascular disease, suggesting that insulin may play a major role in the pathogenesis of arteriosclerosis (Stout and Vallence-Owen, Lancet, 1, 1078 (1969)). Epidemiological studies since then have supported an independent association between hyperinsulinemia and cardiovascular disease (CVD) (Ducimentiere et al., Diabetologia, 19, 205 (1980); Pyörälä et al. Acta Med Scand Suppl., 701, 38 (1985); Després et al., N. Engl. J. Med., 334, 952 (1996); Cavallo-Perin et al., Metabolism, 50, 30 (2001)). Individuals with fasting insulin concentrations above the median level have 5.5 times the odds of developing heart disease than those without hyperinsulinemia after adjustment for a variety of lifestyle and genetic factors (Lamarche et al., JAMA, 279, 1955 (1998)).
Diabetes is a disease in which the body does not produce or properly use insulin, the hormone needed to convert sugar, starches and other food into energy needed for daily life. Type I diabetes and type II diabetes are the two major types of diabetes. Type I diabetes is a disease where the body fails to produce insulin. As a result, people with type I diabetes must take daily insulin shots to stay alive. Type II diabetes results from insulin resistance, which is a condition in which the body fails to make enough or properly use insulin. This insulin resistance is also combined with relative insulin deficiency in type II diabetes. Often, type II diabetes can be controlled through diet, nutrition and lifestyle changes, but many people may also need oral medications and/or insulin to control their diabetes. The cause of diabetes at present is unknown, although both genetics and environmental factors such as obesity and lack of exercise appear to play roles.
Insulin resistance is a state of reduced insulin sensitivity, characterized by an inability of insulin to lower plasma glucose concentrations through suppression of hepatic glucose production and stimulation of glucose utilization in skeletal muscle and adipose tissue. Insulin resistance appears to be involved in the etiology and progression of CVD, type II diabetes and hypertension (Reaven, Diabetes, 37, 1595 (1988)). Epidemiological studies have confirmed the predictive role of hyperinsulinemia and insulin resistance in type II diabetes (Charles et al., Diabetes, 40, 796 (1991); Haffner et al., Diabetes, 41, 715 (1992); Lillioja et al., N. Engl. J. Med., 329, 1988 (1993)) and their strong relationship to hypertension (Haffner et al., Diabetes, 41, 715 (1992); Ferranninni et al., N. Engl. J. Med., 317, 350 (1987)); Swislocki et al., Am. J. Hypertens., 2, 419 (1989); Zavaroni et al., J. Int. Med., 231, 235 (1992)).
Studies in experimental animals have noted that treatment with insulin results in lipid-containing lesions (Stout, Br. Med. J., 3, 685 (1970)), thickening of the arterial wall (Sato et al., Diabetes, 38, 91, (1989)), as well as inhibition of the regression of diet-induced arteriosclerosis (Stamler et al., Circ. Res., 8, 572 (1960)). Furthermore, insulin has been shown to stimulate cholesterol synthesis in cultured arterial smooth muscle cells (Stout, Arteriosclerosis, 27, 271 (1977)) and monocytes, as well as in insulin-treated diabetic patients (Feillet et al., Metabolism, 43, 1233 (1994); Scoppola et al., Diabetologia, 18, 1362 (1995)). Hyperinsulinemia appears to be at the center of metabolic abnormalities including elevated triacylglycerol, depressed HDL-cholesterol, small, dense LDL particles, abdominal obesity and hypertension, and may thus mediate their effect on risk for CVD, type II diabetes and hypertension.
Immigrants representing Asian, African and Hispanic ethnic groups are displaying alarming prevalence of type II diabetes mellitus (AODM) within short periods of time after entering the United States. The Native American populations within the United States presently display nearly 100% prevalence of type II diabetes on some Tribal reservations. Because of an aging immigrant population, Native American population and an aging Caucasian population, researchers have predicted that type II diabetes, and diseases such as cardiovascular disease, kidney disease and blindness, will be seen in epidemic proportions.
Intervention studies in the last several decades have investigated the possibility that the above-mentioned conditions are modifiable and their modification can reduce the incidence and mortality from these conditions. Many trials have investigated the effects of soluble, dietary fiber on these conditions. For example, several trials have been conducted to test the effectiveness of various soluble, dietary fibers to modify cardiovascular disease. Results, however, have been highly variable. Furthermore, despite multiple theories of the mechanism by which soluble fiber acts to decrease serum cholesterol levels and attenuate glucose and insulin response, it is still unclear how such fibers exert their effects.
Dietary fiber is a mixture of three major fractions: structural polysaccharides, structural non-polysaccharides and nonstructural polysaccharides (Schneeman, Food Technol., 40, 104 (1986)). The main components of dietary fiber are further classified based on their solubility in water. The insoluble components include cellulose, lignin, and most hemicelluloses, while the soluble or viscous components are the mucilages (gums), pectin and some hemicelluloses. Fermentability is another property that distinguishes fibers and seems to be linked to their physiologic effects. Generally, very viscous, soluble fibers, such as gums, oat bran and pectin are highly fermentable whereas insoluble fibers, such as cellulose, are only slightly fermentable (Slavin, Dietary Fiber, In: Matarese L S, Gottschlich M M, eds. Contemporary Nutrition Support Practice, New York: WB Saunders, 174-182 (1998)).
Categorization of dietary fiber is related to the method by which fibers are quantified and their respective retrieval under certain physicochemical conditions (Slavin, JADA, 87, 1164 (1987)). However, classifications of fibers have not proved to be especially useful in predicting their behavior in the intact organism, making it important to study various fibers individually and comparatively.
Many food and agricultural byproducts contain a substantial amount of cellulose fibers. Cellulose, a polymer made by plants having an empirical formula ((C6H10O5)n), is an important basic molecular unit of plant fibers and the major polysaccharide in plant cell walls (Falk, S. et al., Physiol. Planetarium, 11, 802 (1958); Frey-Wyssling, A., Deformation and Flow in Biological Systems, Interscience Publishers, Inc., New York (1952); Parrott, M. E. and Thrall, B. R., J. Food Sci., 43, 759 (1978)). The long, thread-like cellulose chains are composed of thousands of glucose molecules, linked together by glycosidic β-1,4 linkages, with intramolecular hydrogen bonding that makes β-linkages extremely stable.
Because of the spatial orientation of the glucose units, cellulose is a linear polymer that can pack very closely together into large, insoluble polymers, which serve a structural role in the plant. For example, the linear polymer of cellulose can form crystalline structures, where the polysaccharide chains are organized into a regular packing arrangement. In addition to the crystalline structure, cellulose can also have amorphous structures, where the polysaccharide chains are in a disorganized state that does not allow for a regular packing arrangement. Furthermore, individual cellulose chains layer themselves on one another, forming “microfibrils,” which contain areas of denser crystalline regions. This arrangement makes cellulose a rather inert entity, unable to participate in chemical reactions unless its fibrous structure is disrupted.
The cellulose fibers can also include lignin, which is a complex polymer of phenylpropane units and hemicellulose. Within the cellulose fibers, cellulose and lignin can be cross-linked. The cross-linking interaction between the glucose molecules of cellulose and lignin makes the cellulose fiber a very stable and resistant material to degradation by weather, microbial attacks and human digestions. Hemicellulose is a polysaccharide that can also be found associated with cellulose, where the branched chains of this molecule bind to cellulose microfibrils, together with pectins, forming a network of cross-linked fibers.
The practical use of soluble fiber is limited by the untoward side effects associated with increased consumption. Studies have reported gastrointestinal discomfort, including flatulence, bloating, nausea, feeling of fullness, and loose stools. In addition, many soluble fibers have marginal palatability (e.g., guar gum) or are difficult to consume frequently because of their energy content (e.g., oatmeal). These issues limit the quantity of soluble fiber a person can consume, and thus, limit the amount of benefit to be experienced.